标题: An MD's Account of His Use of SSRI and Wegovy [打印本页] 作者: choi 时间: 9-14-2023 14:42 标题: An MD's Account of His Use of SSRI and Wegovy Aaron E Carroll, What Obesity Drugs and Antidepressants Have in Common? The more misunderstood the condition, the more we moralize its treatment. New York Times, Sept 10, 2023 (Sunday), at page 12 of SundayOpinion section. https://www.nytimes.com/2023/09/ ... essants-stigma.html
My comment:
(a) Under his name in the NYT essay is this introduction: "Dr Carroll is the chief health officer of Indiana University and writes often on health policy.
An MD, he is Distinguished Professor of Pediatrics of Indiana University. His photos do not look obese -- quite normal to me.
(b) Please stop reading after the paragraph that starts with "I’ve lost 15 pounds in the last five weeks
I am only interested in how he felt when he took medicines, not moralizing.
(c) "we know that selective serotonin reuptake inhibitors, or SSRIs, leave more serotonin floating around your neurons in your brain, but we don't fully understand how or why that makes a difference. We also can't explain why some people benefit from SSRIs and others do not."
(i) I will begin with the last sentence. Not all drugs are effective on everybody. This is common sense.
(ii)
(A) Andrew Chu and Roopma Wadhwa, Selective Serotonin Reuptake Inhibitors. StatPearls, last updated on May 1, 2023. https://www.ncbi.nlm.nih.gov/books/NBK554406/
Quote:
Mechanism of Action: "The therapeutic actions of SSRIs have their basis on increasing deficient serotonin that researchers postulate as the cause of depression in the monoamine hypothesis [which , in other words, theorizes that somehow depressed person does not produce enough serotonin in his brain or some part of it]. As the name suggests, SSRIs exert action by inhibiting the reuptake of serotonin, thereby increasing serotonin activity. Unlike other classes of antidepressants, SSRIs have little effect on other neurotransmitters * * * SSRIs inhibit the serotonin transporter (SERT) at the presynaptic axon terminal. By inhibiting SERT, an increased amount of serotonin * * * remains in the synaptic cleft and can stimulate postsynaptic receptors for a more extended period.
Administration: "SSRIs are only available orally * * *
section 6 Mechanism of action: "In the brain, messages are passed from a nerve cell to another via a chemical synapse, a small gap between the [nerve] cells. The presynaptic cell that sends the information releases neurotransmitters including serotonin into that gap. The neurotransmitters are then recognized by receptors on the surface of the recipient postsynaptic cell, which upon this stimulation, in turn, relays the signal. About 10% of the neurotransmitters are lost in this process; the other 90% are released from the receptors and taken up again by monoamine transporters into the sending presynaptic cell, a process called reuptake. * * * Owing to the lack of a widely accepted comprehensive theory of the biology of mood disorders, there is no widely accepted theory of how these changes lead to the mood-elevating and anti-anxiety effects of SSRIs. * * * [In contrast,] MDMA leads to an excess serotonin release in a short run. This could explain the absence of a 'high' by antidepressants [such as SSRIs]
MDMA is the acronym for "3,4-Methylenedioxymethamphetamine," whose street names are ectasy or molly. MDMA is a kind of amphetamine and methamphetamine. In terms of cheical structure, the difference between
methamphetamine https://en.wikipedia.org/wiki/Methamphetamine
and amphetamine is that the former has an additional methyl group (-CH3) attached to the nitrogen atom.
(d) "I asked my doctor to write me a prescription for one of the new injectable obesity drugs. He warned me that it was approved at this time only for people with diabetes, and since I didn't suffer from that, this would be off-label use and wouldn't be covered by insurance."
(i) semaglutide https://en.wikipedia.org/wiki/Semaglutide
("sold under the brand names Ozempic, Wegovy and Rybelsus" by the same (Danish) pharmaceutical company, Novo Nordisk)
FDA approved ozempic for diabetic treatment, and wegovy for obesity treatment. The ozempic, wegovy and rybelsus all have the same active ingredient (whose scientific name is semaglutide), but wegovy has a higher dosage than ozembic (both of which are injectable only), whereas rybelsus is tablet for oral use. The wegovy is injected subcutaneously once a week (every seven days) because its half-life in blood is seven days.
In comparison, tirzepatide (made by Eli Lilly) is injectable subcutaneously (not oral), which FDA approved only for diatetic treatment. However Eli Lilly is seeking approval from FDA to treat obesity, too.
Both semaglutide and tirzepatide are analogs of human GLP-1 (short for Glucagon-like peptide-1), in terms of chemical structures.
Wiktionary says glutide is from "glucagon-like peptide analog."
As dar as I know, nobody know the exact mechanism how semaglutide works. In humans, GLP-1 is quickly destroyed by enzymes that are present everywhere; that is why analogs are needed to elude these enzymes. Where do analogs act” In the stomach, in the brain? Nobody knows.
(ii) "He warned me that it was approved at this time only for people with diabetes, and since I didn't suffer from that, this would be off-label use"
A drawback is your medical insurance company will not pay for the drug. But a physician can write in the medical chart that he or she prescribes according to FDA: however a patient uses it is none of his business.
A drawback is your medical insurance company will not pay for the drug. But a physician can write in the medical chart that he or she prescribes according to FDA: however a patient uses it is none of his business.
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We like to think we understand the drugs we take, especially after rigorous trials have proved their efficacy and safety. But sometimes, we know only that medications work; we just don’t know why.
Recently, I’ve faced this conundrum regarding drugs for mental health conditions and obesity, two heavily stigmatized health issues with causes and treatments that science doesn’t fully comprehend.
Until a few years ago, I had controlled my depression and anxiety through decades of counseling. I was reluctant to try medications because the medical understanding of them seemed vague. For instance, we know that selective serotonin reuptake inhibitors, or S.S.R.I.s, leave more serotonin floating around your neurons in your brain, but we don’t fully understand how or why that makes a difference. We also can’t explain why some people benefit from S.S.R.I.s and others do not. Because of this, many people still believe those who take them don’t really need them.
I also believed that, if I was strong enough, I didn’t need medication. But in 2021, when I was under a substantial amount of stress, I had a panic attack on vacation and fell partway down a mountain. I was airlifted to a hospital, alarming my wife and friends. It was clear I wasn’t OK.
My physician recommended sertraline, an older but widely used S.S.R.I. While I was skeptical that it would make a difference, I tried it.
I was wrong to doubt. It’s had a remarkable effect on my mood, and almost everyone around me noticed the difference. I was more optimistic, friendlier and more engaging. I was forced to reconsider why I had avoided taking the medication for so long. I think it’s because — even though I realize this isn’t true — taking it felt like an admission of failure.
Because I didn’t know the exact mechanism that caused my anxiety to be uncontrollable (and no one else did either), it seemed as if I must be cheating to use a drug that greatly helped my situation. It felt like a crutch or a shortcut. Especially because, even as a doctor, I can’t explain why the medication works for me or anyone else.
I’ve recently faced a similar scenario with new drugs for obesity. I’ve struggled with my weight for most of my life. I’ve always been overweight, and in the last few years, I’ve slipped into obesity, according to my body mass index. I exercise regularly and carry the weight well, but it bothers me immensely. It especially troubles me because I have a fair amount of self-discipline and eat quite healthfully.
Though I’ve tried every diet, nothing has really helped. I’d lose up to 10 pounds and then plateau until my weight crept back up.
Because I am so careful about what I eat, my weight has not yet led to any other health consequences. But I know what could happen if I stop being mindful. My father was morbidly obese. It led to a lower quality of life and mental health issues and probably contributed to his death a few years ago.
Despite all the advances in science, we don’t know why some people, even when they try desperately, can’t seem to lose weight. Because of that, we often assume it must be a lack of willpower. I begged my father, who was also a physician, to lose weight, and he never could. In the back of my mind, I, like many others, blamed him for his failures and considered it a lack of resolve.
I blamed myself, too. I became so disheartened at my inability to affect my weight that it harmed my mental health. I felt like a failure, which led to self-hatred and anger.
Five weeks ago, I went on a walk with a friend who had just lost a younger brother to heart disease. It was a reminder that time is limited and I should make use of it more wisely. I asked my doctor to write me a prescription for one of the new injectable obesity drugs. He warned me that it was approved at this time only for people with diabetes, and since I didn’t suffer from that, this would be off-label use and wouldn’t be covered by insurance. These drugs are expensive, but I was determined to see what would happen if I took one.
It is hard to explain what life is like on this medication to people who don’t have trouble controlling their weight. I’m not hungry all the time. I’m not thinking about food incessantly. I’m not obsessing about what I wish I could eat and what I can’t. My mental health, and even my temperament, improved so much that my whole family rejoiced.
I’ve lost 15 pounds in the last five weeks, and I’ve done it with ease. It can’t just be because I’m eating much less, because I haven’t reduced my caloric intake that much. But like everyone else, including scientists, I have no idea why these drugs work so well.
Before writing this essay, I had told just a few people I’m on the drug. I think it’s because, on some level, I still feel shame. I felt the same when I finally started taking an antidepressant.
Mental health disorders and obesity fall into a bucket of diagnoses that, amid a lack of complete knowledge of their causes, are subject to societal moralizing and stigma. We make assumptions that people with depression aren’t trying hard enough, that people with obesity lack willpower. These stigmas are then compounded by a limited understanding of how their treatments work, leading to further judgments of people who seek them.
This is especially true if there’s no clear endpoint for treatment. I’ve heard so many thoughtful people argue against using these injectable drugs for weight loss because “people often regain the weight if they stop taking them.” Of course they do. Something is off balance with them that these drugs are correcting. We don’t know what it is, but the drugs are compensating for it, not curing people permanently.
As I’ve written before, I’ve had ulcerative colitis for almost 30 years. The medication I take to keep me in remission has a small, but greater than zero, chance of shutting down my blood marrow, yet the upsides are hard to overemphasize. I will be on that drug for the rest of my life. I’m OK with that, and no one, including me, has ever questioned if it’s a good idea to take it because I’ll never be able to quit.
We don’t assume that people with Type 1 diabetes who need to be on insulin, or people on thyroid medication, should have to stop. There are many other examples of conditions whose sufferers must undergo treatments for decades or more.
The mechanisms for those diseases and disorders are usually better understood, though; they fix problems we’ve mapped out pretty clearly and are not perceived as being the result of a personal deficiency. It’s when there’s doubt and stigma that we question the need and the longevity.
I’m sure these obesity drugs won’t work for everyone — they won’t overcome bad eating habits or many other issues. I am also aware that we don’t know their long-term effects. Most important, I know I’m privileged that I can afford to pay for them out of pocket.
What we should focus on is their potential to improve lives significantly, much as they have for me. Medical treatments should not be dismissed just because we don’t fully grasp their mechanisms; people who use them are not cheating.